Tnpo3 controls splicing of the pre-mRNA encoding the canonical TCR alpha chain of iNKT cells

Unconventional T cells, such as innate natural killer T cells (iNKT) cells, are an important part of vertebrate immune defences. iNKT recognise glycolipids through a T cell receptor (TCR) that is composed of a semi-invariant TCR alpha chain, paired with a restricted set of TCR beta chains. Here, we show that splicing of the cognate Trav11-Traj18-Trac pre-mRNA encoding the characteristic V alpha 14J alpha 18 variable region of this semi-invariant TCR depends on the presence of Tnpo3. The Tnpo3 gene encodes a nuclear transporter of the beta-karyopherin family whose cargo includes various splice regulators. The block of iNKT cell development in the absence of Tnpo3 can be overcome by transgenic provision of a rearranged Trav11-Traj18-Trac cDNA, indicating that Tnpo3 deficiency does not interfere with the development of iNKT cells per se. Our study thus identifies a role for Tnpo3 in regulating the splicing of the pre-mRNA encoding the cognate TCR alpha chain of iNKT cells. iNKT cells recognise glycolipids via their T cell receptors. Here the authors implicate tnpo3 in the regulation of splicing of pre-mRNA encoding cognate TCR alpha chain for iNKT cells.

Automated summary

Unconventional T cells, such as iNKT cells, play an important role in vertebrate immune defenses. The study suggests that Tnpo3 is involved in regulating the splicing of pre-mRNA encoding the characteristic TCR alpha chain of iNKT cells.